ABSTRACT Cortical processing of sensory information plays a critical role in sensory discrimination, object recognition and memory. Cortical sensory processing has been shown to be highly dynamic, with past experience, current context and expectations shaping how the world is perceived on a moment by moment basis. Disorders of sensory processing constitute a major component of impairments induced by CNS disease and aging, as well as congenital disorders such as schizophrenia and autism. In the olfactory sensory (piriform) cortex diverse stimulus features are synthesized into perceptual wholes through afferent and intrinsic fiber convergence and plasticity, allowing familiar odor objects to be remembered. The intrinsic, association fiber system in priform cortex is extensive, and based on anatomical data and new physiological data supported by an R21 to the co-PI's, plays a role in shaping cortical ensemble activity in response to odorant stimuli. Thus, our data demonstrate that odorants evoke distributed unit ensemble activity throughout anterior piriform cortex (aPCX), with individual components of the ensemble contributing to multiple odorant representations. In the present proposal, which extends the R21-supported research, we propose to address three previously untested hypotheses regarding cortical ensemble function in olfaction using multi-electrode array and paired single-unit recording in anesthetized and awake rats. Aim 1 will test the hypothesis that cell ensemble membership size and the probability of correlated activity in paired single-units will be greater in the posterior PCX (pPCX) than in aPCX due to the more extensive intrinsic excitatory association fiber system in pPCX. Aim 2 will test the hypothesis that manipulations of the neuromodulators ACh and NE to PCX, which selectively affect intrinsic fiber synaptic efficacy, will modulate ensemble membership size, odorant specificity and probability of correlated activity in paired single-units. Finally, Aim 3 will test the hypothesis that behavioral state will modulate ensemble size, odorant specificity and probability of correlated activity in cell pairs, potentially via a cholinergic or noradrenergic mechanism. Together, these aims will begin to explore how cortical ensembles merge the myriad odorant features encoded by peripheral circuits into odorant objects, and how attention and arousal may modulate odor discrimination. PUBLIC HEALTH RELEVANCE Cortical processing of information plays a critical role in sensory perception, memory, movement and cognition. Thus, understanding how circuits within the cortex process information is important for understanding and treating disorders of information processing. This proposal takes advantage of a relatively simple cortical circuit (the piriform cortex) performing relatively complex information processing tasks (odor object discrimination) to explore how groups of neurons work together as an ensemble to interpret sensory input.